Vascular blood flow is now most commonly occluded during surgery by either clamping or ligation. Blood vessels are lined internally with a single layer of endothelial cells which are joined laterally by tight junctions and which overlie a layer of smooth muscle cells. This endothelial lining forms a permeability barrier to prevent the passage of large molecules between the blood and the extra corporeal space. Clamping or ligation results in trauma to the vessel and disruption of the endothelial cell permeability barrier (Barone GW, Conerly JM, Farley PC, Flanagan TL, Kron IL, Surgery 105:465-471, 1989; Moore WM, Manship LL, Bunt TJ, Am. Surg. 5:392-400, 1985; Margovsky AI, Lord RSA, Chambers AJ, Aust. N. Z. J. Surg. 67:448-451, 1997). In one study, these effects persisted for at least two weeks after a clamping period of only five minutes (Jackiewicz TA, McGeachie JK, Tennant M, Microsurg. 17:674-680, 1996). Compromising the permeability barrier allows the passage of factors in the blood which promote smooth muscle cell growth such as the platelet-derived growth factor (Jackiewicz TA, McGeachie JK, Tennant M, Microsurg. 17:674-680, 1996). Clamp injury can therefore cause later formation of atherosclerotic plaque and stenosis at the clamp site (Margovsky AI, Lord RSA, Chambers AJ, Aust. N. Z. J. Surg. 67:448-451, 1997). In addition, clamping can cause immediate peri-operative complications such as arterial dissection (Litchford B, Okies JE, Sugimura S, Starr A, J. Thorac. Cardiovasc. Surg. 72:709-713, 1976) or thrombosis due to embolization of atherosclerotic plaque to distal portions of the circulation (Archie JP Jr, Am. Surg. 54:167-168, 1988). Diseased vessels, such as those encountered during coronary artery revascularization, are especially prone to both immediate and long-term deleterious effects of clamping or ligation (Manship LL, Moore WM, Bynoe R, Bunt TJ, Am. Surg. 5:401-406, 1985). Noncompressible hemorrhage continues to be a primary cause of death in both military and civilian trauma (Bellamy R F. Mil. Med. 149:55-62, 1984; Sauaia A et al J. Trauma 38:185-193, 1995). Currently there is no treatment short of surgery for severe abdominal bleeding resulting from either blunt or penetrating injury. Vascular injuries in the region of the groin continue to be largely untreatable.
The use of magnetic particles for different applications in medicine has been reported for a long time. The most representative examples follow. U.S. Pat. No. 4,247,406 (Widder et al, 1981), U.S. Pat. No. 4,345,588 (Widder et al, 1982), U.S. Pat. No. 4,331,654 (Morris et al, 1982), U.S. Pat. No. 4,501,726 (Schroder et al, 1985), U.S. Pat. No. 4,690,130 (Mirell SG, 1987), U.S. Pat. No. 5,411,730 (Kirpotin et al, 1995),U.S. Pat. No. 5,427,767 (Kresse et al, 1995),U.S. Pat. No. 5,753,477 (Chan, 1998), and U.S. pat. application Ser. No. 0219785 A 1 (Hallahan et al., 2003) disclose the use of magnetic carriers for localized delivery of therapeutic or diagnostic agents. U.S. Pat. No. 5,314,679 (Lewis et al, 1994) and U.S. patent application Ser. No. 09/852,421 (Unger, 2003) disclose the use of magnetic particles as contrast agents for magnetic resonance imaging. U.S. patent application Ser. No. 10/389,708 (Schwartz et al, 2003) discloses a method to embolize a vascular site using a microparticle comprised of a hydrolyzable crosslinked hydrogel. In this patent application, magnetic particles are also included as contrast agents in the hydrogel for magnetic resonance imaging. The mechanism of embolization here is the hydrolyzation of the crosslinked hydrogel. U.S. Pat. No. 6,303,487 B1 (Consigny PM, 2001) discloses the use of magnetic particles in the focal delivery of cells.
U.S. Pat. No. 6,364,823 B1 (Garibaldi et al, 2002) discloses the use of magnetic particles for controlling the delivery of an embolic agent to a vascular defect. The purpose of Garibaldi's work is the delivery of embolic materials to the site of the vascular defect using magnetic means. A liquid embolic agent is provided with a magnetic constituent to be drawn into the defect using an applied magnetic field. The embolic agent, after reaching the vascular defect, precipitates a polymer which in combination with a glue, seals the vascular defect. In essence, the purpose of the magnetic material is to deliver the embolic agent with the precipitating polymer and glue to the site of the vascular defect. This application is similar to the targeted delivery of pharmaceutical agents to a particular site except that the agent here is an embolic material. Basically, in the above applications, magnetic particles have been used as a carrier to take a pharmaceutical or embolic agent to a particular location.
U.S. Pat. No. 5,236,410 (Granov et al, 1993) discloses a method of treatment for a tumor using a magnetically hard, radio-opaque, ferromagnetic material suspended in an oil solution of an oil-soluble anti-tumor substance. A suspension of demagnetized ferromagnetic particles in an oil solution of an anti-tumor substance is drawn into the area of the tumor using an applied magnetic field. The ferromagnetic particles become remagnetized and, because of the high residual magnetism of the hard ferromagnetic material, form a porous body of aggregates at the tumor area. One purpose of the oil-suspended hard ferromagnetic material is to deliver as a carrier the oil-soluble anti-tumor substance to the tumor area and another purpose is to retain it within the tumor area by embolization of the hard ferromagnetic material. The major purpose of the oil-suspended hard ferromagnetic material, however, is for its use in hyperthermia. The distinction of Granov's method, compared to other hyperthermia methods or chemotherapy, is that Granov utilizes both chemotherapy and hyperthermia in trying to produce necrosis of the tumor tissue. U.S. Pat. No. 6,149,576 (Gray et al, 2000) discloses the use of a ferromagnetic material to treat a tumor tissue by producing hyperthermia with the application of a rotational magnetic field.
U.S. Pat. No. 4,364,377 (Smith F W, 1982) discloses a method to repair or fix a lesion in the gastrointestinal tract. Under his method a ferromagnetic tamponading mass is introduced into the gastrointestinal tract near a bleeding lesion by the use of a catheter. The tamponading mass forms near the lesion due to the high residual magnetism of the ferromagnetic particles. An external magnetic field generator is used to move the tamponading mass and position it to close the lesion hole. The tamponading mass stops the bleeding once it has been positioned at the lesion. In Smith's method the ferromagnetic tamponading mass is introduced into the gastrointestinal tract and the tamponading mass is formed without the use of the external magnetic field. The main purpose of the external magnetic field generator is to move the tamponading mass to the position of the lesion.
The present invention relates to the occlusion of blood vessels to stop the flow of blood, especially during elective or emergency surgical procedures or following traumatic injury. The invention is a safer alternative vascular occlusion method which has none of the injurious effects of clamping or ligation described above.